Functional and Therapeutic Relevance of Rho GTPases in Innate Immune Cell Migration and Function during Inflammation: An In Silico Perspective
Systematic regulation of leukocyte migration to the site of infection is a vital step during immunological responses. Improper migration and localization of immune cells could be associated with disease pathology as seen in systemic inflammation. Rho GTPases act as molecular switches during inflamma...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/6655412 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849399214630502400 |
|---|---|
| author | Pankaj Dipankar Puneet Kumar Shiba Prasad Dash Pranita P. Sarangi |
| author_facet | Pankaj Dipankar Puneet Kumar Shiba Prasad Dash Pranita P. Sarangi |
| author_sort | Pankaj Dipankar |
| collection | DOAJ |
| description | Systematic regulation of leukocyte migration to the site of infection is a vital step during immunological responses. Improper migration and localization of immune cells could be associated with disease pathology as seen in systemic inflammation. Rho GTPases act as molecular switches during inflammatory cell migration by cycling between Rho-GDP (inactive) to Rho-GTP (active) forms and play an essential role in the precise regulation of actin cytoskeletal dynamics as well as other immunological functions of leukocytes. Available reports suggest that the dysregulation of Rho GTPase signaling is associated with various inflammatory diseases ranging from mild to life-threatening conditions. Therefore, it is crucial to understand the step-by-step activation and inactivation of GTPases and the functioning of different Guanine Nucleotide Exchange Factors (GEFs) and GTPase-Activating Proteins (GAPs) that regulate the conversion of GDP to GTP and GTP to GDP exchange reactions, respectively. Here, we describe the molecular organization and activation of various domains of crucial elements associated with the activation of Rho GTPases using solved PDB structures. We will also present the latest evidence available on the relevance of Rho GTPases in the migration and function of innate immune cells during inflammation. This knowledge will help scientists design promising drug candidates against the Rho-GTPase-centric regulatory molecules regulating inflammatory cell migration. |
| format | Article |
| id | doaj-art-9d6d2d73ec194ec8afeea1e014c9166c |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-9d6d2d73ec194ec8afeea1e014c9166c2025-08-20T03:38:23ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/66554126655412Functional and Therapeutic Relevance of Rho GTPases in Innate Immune Cell Migration and Function during Inflammation: An In Silico PerspectivePankaj Dipankar0Puneet Kumar1Shiba Prasad Dash2Pranita P. Sarangi3Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, IndiaDepartment of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, IndiaDepartment of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, IndiaDepartment of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, IndiaSystematic regulation of leukocyte migration to the site of infection is a vital step during immunological responses. Improper migration and localization of immune cells could be associated with disease pathology as seen in systemic inflammation. Rho GTPases act as molecular switches during inflammatory cell migration by cycling between Rho-GDP (inactive) to Rho-GTP (active) forms and play an essential role in the precise regulation of actin cytoskeletal dynamics as well as other immunological functions of leukocytes. Available reports suggest that the dysregulation of Rho GTPase signaling is associated with various inflammatory diseases ranging from mild to life-threatening conditions. Therefore, it is crucial to understand the step-by-step activation and inactivation of GTPases and the functioning of different Guanine Nucleotide Exchange Factors (GEFs) and GTPase-Activating Proteins (GAPs) that regulate the conversion of GDP to GTP and GTP to GDP exchange reactions, respectively. Here, we describe the molecular organization and activation of various domains of crucial elements associated with the activation of Rho GTPases using solved PDB structures. We will also present the latest evidence available on the relevance of Rho GTPases in the migration and function of innate immune cells during inflammation. This knowledge will help scientists design promising drug candidates against the Rho-GTPase-centric regulatory molecules regulating inflammatory cell migration.http://dx.doi.org/10.1155/2021/6655412 |
| spellingShingle | Pankaj Dipankar Puneet Kumar Shiba Prasad Dash Pranita P. Sarangi Functional and Therapeutic Relevance of Rho GTPases in Innate Immune Cell Migration and Function during Inflammation: An In Silico Perspective Mediators of Inflammation |
| title | Functional and Therapeutic Relevance of Rho GTPases in Innate Immune Cell Migration and Function during Inflammation: An In Silico Perspective |
| title_full | Functional and Therapeutic Relevance of Rho GTPases in Innate Immune Cell Migration and Function during Inflammation: An In Silico Perspective |
| title_fullStr | Functional and Therapeutic Relevance of Rho GTPases in Innate Immune Cell Migration and Function during Inflammation: An In Silico Perspective |
| title_full_unstemmed | Functional and Therapeutic Relevance of Rho GTPases in Innate Immune Cell Migration and Function during Inflammation: An In Silico Perspective |
| title_short | Functional and Therapeutic Relevance of Rho GTPases in Innate Immune Cell Migration and Function during Inflammation: An In Silico Perspective |
| title_sort | functional and therapeutic relevance of rho gtpases in innate immune cell migration and function during inflammation an in silico perspective |
| url | http://dx.doi.org/10.1155/2021/6655412 |
| work_keys_str_mv | AT pankajdipankar functionalandtherapeuticrelevanceofrhogtpasesininnateimmunecellmigrationandfunctionduringinflammationaninsilicoperspective AT puneetkumar functionalandtherapeuticrelevanceofrhogtpasesininnateimmunecellmigrationandfunctionduringinflammationaninsilicoperspective AT shibaprasaddash functionalandtherapeuticrelevanceofrhogtpasesininnateimmunecellmigrationandfunctionduringinflammationaninsilicoperspective AT pranitapsarangi functionalandtherapeuticrelevanceofrhogtpasesininnateimmunecellmigrationandfunctionduringinflammationaninsilicoperspective |